Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a receptor for capsaicin and a non-selective cation channel structurally related to members of the transient receptor potential (TRP) family of ion channels. TRPV1 is modulated by various physical and chemical stimuli such as mild voltage, endogenous lipids, small proteins, pH, and capsaicin, and is also activated by increases in temperature in the noxious range, indicating it functions as a transducer of painful thermal stimuli in vivo. Due to its sensitivity to some noxious stimuli, TRPV1 is an excellent therapeutic target especially for pain. However, it was previously unknown how capsaicin interacts with TRPV1 or drives ion channel activation.